FUT9 - the dedicated Lewis-x synthase, structurally solved, and untouched by the KMT2A literature

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[]

{
  "chronos_mean_kmt2a_rearranged": 0.1113,
  "chronos_mean_other_leukaemia": 0.0816,
  "difference": 0.0297,
  "pan_essentiality_all_lines": 0.1106,
  "selectivity_rank": 12831,
  "rank_denominator": 17728,
  "provenance": "Joined 2026-09-21 from analyses/depmap-kmt2a-selective-scan-full (generated 2026-09-19T10:12:06Z), the project's own genome-wide scan over 11 KMT2A-rearranged and 43 other leukaemia DepMap lines. NOT re-fetched and NOT independent of that scan: every caveat it carries applies here, including that the KMT2A-rearranged arm is a small number of lines drawn from nine individuals, that the rank denominator is 17,728 genes, and that a difference is not a dependency. Added because only 26 of 308 gene entries carried this number, which made any KMT2A-selectivity question answerable for 8% of the corpus.",
  "how_to_read": "A negative difference means MORE required in KMT2A-rearranged lines than in other leukaemia lines. A rank near 17,728 is ANTI-selective. Neither is evidence of a fusion-driven dependency on its own: check pan_essentiality_all_lines before calling anything selective, and note that a paralogue-redundant gene can score near zero for reasons that have nothing to do with this disease - see ana-the-paralogue-redundancy-excuse-is-not-tested-and-my-proxy-decided-the-answer."
}

{
  "subcellular": "GOLGI APPARATUS, TRANS-GOLGI NETWORK MEMBRANE, single-pass type II signal-anchor. UniProt Q9Y231 (fetched live 2026-09-21) carries 'Golgi apparatus, trans-Golgi network membrane' on ECO:0000269 PubMed:18395013, a 'Golgi apparatus membrane' value at ECO:0000250 from O88819, and the topology 'Single-pass type II membrane protein' at ECO:0000250 from Q6P4F1; the feature table carries one helical transmembrane segment at residues 12-32 annotated 'Signal-anchor for type II membrane protein' [E_q93_fut9_loc1].",
  "subnuclear": "NOT APPLICABLE. FUT9 is a type II single-pass Golgi membrane glycosyltransferase: a short cytoplasmic N-terminus, a signal-anchor transmembrane helix at 12-32, and the catalytic domain in the Golgi LUMEN, where its substrates and its GDP-fucose donor are. There is no soluble nuclear species and no annotated NLS. Recorded as a CATEGORY EXCLUSION so it stays OUT of the denominator of proteins whose subnuclear compartment nobody has measured - the handling given to HLA-A, NRAS, B2M, PROM1, CD33, ELOVL1 and SEPTIN2 in earlier tranches, and to HLA-B in this one. THE DISPATCH BRIEF PREDICTED THIS OUTCOME FOR FUT9 AND THE PREDICTION IS CONFIRMED.",
  "not_applicable_reason": "type II single-pass Golgi membrane glycosyltransferase, signal-anchor transmembrane 12-32, catalytic domain in the Golgi lumen, no nuclear pool and no annotated NLS",
  "RULE_91_PASSES_HERE_AND_THE_CITATION_IS_BETTER_THAN_THE_ANNOTATION": "PubMed:18395013 is 'Human fucosyltransferase IX: specificity towards N-linked glycoproteins and RELEVANCE OF THE CYTOPLASMIC DOMAIN IN INTRA-GOLGI LOCALIZATION' - a paper whose title contains the localisation question and whose finding is finer than the annotation: the CYTOPLASMIC DOMAIN determines WHERE WITHIN THE GOLGI the enzyme sits [E_q93_fut9_loc2]. This is the only entry in the tranche whose UniProt compartment citation is a dedicated, on-point, sub-organellar localisation study. The record is otherwise the best-cited in this tranche for exactly the reason this entry already records: FUT9 is the cleanest identifier on its beat, with no gene synonyms and no previous symbols.",
  "AND_TWO_ANNOTATION_ODDITIES_WORTH_RECORDING": "(1) THE TOPOLOGY IS INFERRED FROM A DIFFERENT ENZYME FAMILY. 'Single-pass type II membrane protein' is ECO:0000250 from Q6P4F1, which was fetched and read back in the same session: it is POFUT3 (OFUT3_HUMAN), GDP-fucose PROTEIN O-fucosyltransferase 3, 479 aa, an ENDOPLASMIC RETICULUM membrane enzyme - a different length, a different family and a different compartment. (2) THE MOUSE-HUMAN INFERENCE IS CIRCULAR. Mouse Fut9 (O88819, 359 aa) carries its trans-Golgi-network value as ECO:0000250 FROM Q9Y231, the human record, while the human record's TGN value is the experimental one. So mouse is inferred from human here, the reverse of the SGF29, CTR9, CSNK2A2 and NASP chains this beat found, and a reader who checked only the mouse record would find a by-similarity call with no source in its own species [E_q93_fut9_loc1].",
  "how_shown": "the TGN localisation is from a dedicated intra-Golgi localisation study using FUT9 cloned from NT2N neurons and overexpressed in HeLa (PMID 18395013); the topology is by similarity from an unrelated ER enzyme; the transmembrane segment is annotated in the feature table",
  "systems": "HeLa cells overexpressing FUT9 cloned from NT2N neurons. No haematopoietic cell for the localisation, and no leukaemic cell of any kind",
  "node": "localization-dpy30-trans-golgi-network-pool"
}

{
  "HAEMATOPOIETIC_AND_UNUSUALLY_PRECISE_FOR_THIS_BEAT": "MATURE GRANULOCYTES, AND EXPLICITLY NOT MONOCYTES. UniProt Q9Y231's tissue comment reads: strongly expressed in forebrain and stomach, lower in spleen and PERIPHERAL BLOOD LEUKOCYTES, absent from small intestine, colon, liver, lung, kidney, adrenal cortex and uterus (PubMed:10386598); HIGHLY EXPRESSED IN GRANULOCYTES, NOT EXPRESSED IN MONOCYTES (PubMed:11278338) [E_q93_fut9_loc1][E_q93_fut9_loc3].",
  "and_the_division_of_labour_is_measured_not_assumed": "Nakayama and colleagues set out to determine which alpha1,3-fucosyltransferase makes the CD15 epitope in each leukocyte subpopulation and found that FUT9 has 20-FOLD STRONGER ACTIVITY FOR CD15 SYNTHESIS THAN FUT4, while FUT4 has 4.5-fold stronger activity for CDw65 synthesis than FUT9; by competitive RT-PCR, FUT9 IS STRONGLY EXPRESSED IN MATURE GRANULOCYTES AND PERIPHERAL BLOOD MONONUCLEAR CELLS BUT NOT IN MONOCYTES, and the conclusion is that CD15 EXPRESSION IN MATURE GRANULOCYTES IS DETERMINED BY FUT9 WHILE IN PROMYELOCYTES AND MONOCYTES IT IS DETERMINED BY FUT4 [E_q93_fut9_loc3].",
  "why_this_matters_to_this_graph_specifically": "Brief rule 69 records that CD15 is a PREVIOUS OFFICIAL SYMBOL OF FUT4 and that assigning the 24-entry Lewis-x antigen to FUT4 would be a confident wrong gene assignment, because FUT4 helps BUILD Lewis-x rather than encoding it. This paper is the measurement behind that caution and it makes it sharper: the enzyme responsible for CD15 DEPENDS ON THE MATURATION STAGE OF THE CELL. So 'CD15-positive' in a leukaemia flow panel is not one biochemical fact, and which fucosyltransferase built the epitope on a given blast is a function of where that blast sits on the myeloid maturation axis - a genuinely differentiation-state-dependent surface marker.",
  "in_this_disease": "NOTHING. This entry's existing content records that FUT9 is untouched by the KMT2A literature, and the bounded queries here confirm a total zero against every fusion clause tried. CD15 itself is well documented on KMT2A-rearranged blasts in this graph's antigen entries, so the gap is specifically enzymatic: nobody has asked which fucosyltransferase makes CD15 on a KMT2A-rearranged blast."
}

{
  "STATE_IS_MYELOID_MATURATION_STAGE_AND_IT_SWITCHES_THE_ENZYME": "The same epitope is built by different enzymes at different maturation stages - FUT9 in mature granulocytes, FUT4 in promyelocytes and monocytes [E_q93_fut9_loc3]. That is a differentiation-state-dependent biosynthetic switch, and it is the only cell-state statement this gene has.",
  "the_consequence_for_a_differentiation_blocked_blast": "This disease's defining state is a DIFFERENTIATION BLOCK, and the FUT9/FUT4 division of labour is indexed to maturation. A blast arrested before the granulocytic stage at which FUT9 takes over would be expected to make CD15 through FUT4 rather than FUT9 - which is a prediction, not a finding, and it is testable from existing expression data because the two genes are separately quantified in any RNA-seq. THIS ENTRY DOES NOT ASSERT IT; it records that the inference is available and unmade.",
  "bounded": "No FUT9 measurement of any kind - expression, activity or localisation - exists in a KMT2A-rearranged cell."
}

{
  "date": "2026-09-21",
  "tool": "NCBI E-utilities esearch, db=pubmed",
  "run_by": "Q93",
  "queries": [
    {
      "query": "(\"FUT9\"[tiab] OR \"fucosyltransferase IX\"[tiab] OR \"alpha1,3-fucosyltransferase IX\"[tiab])",
      "querytranslation": "\"FUT9\"[Title/Abstract] OR \"fucosyltransferase IX\"[Title/Abstract] OR \"alpha1,3-fucosyltransferase IX\"[Title/Abstract]",
      "count": 83,
      "role": "operand control"
    },
    {
      "query": "(gene clause) AND (twelve-term subnuclear clause)",
      "count": 0,
      "bound_not_reproducible_as_stored": "NOT REPRODUCIBLE AS STORED, flagged 2026-09-23. This `query` field records a SUMMARY of the search rather than the search: the clause text it names was never written down, so the string cannot be re-run and this bound could not be included in the cycle-71 audit that re-ran 40 of the corpus's other zero-bounds against the live index (all 40 still returned zero). The clauses have deliberately NOT been reconstructed - guessing them would manufacture a query that was never run, which is worse than an abbreviated one because it would look auditable. This flag does not dispute the count or the absence; it records that this particular bound is not independently checkable."
    },
    {
      "query": "(gene clause) AND (nine-term KMT2A/MLL fusion clause)",
      "count": 0,
      "bound_not_reproducible_as_stored": "NOT REPRODUCIBLE AS STORED, flagged 2026-09-23. This `query` field records a SUMMARY of the search rather than the search: the clause text it names was never written down, so the string cannot be re-run and this bound could not be included in the cycle-71 audit that re-ran 40 of the corpus's other zero-bounds against the live index (all 40 still returned zero). The clauses have deliberately NOT been reconstructed - guessing them would manufacture a query that was never run, which is worse than an abbreviated one because it would look auditable. This flag does not dispute the count or the absence; it records that this particular bound is not independently checkable."
    },
    {
      "query": "(gene clause) AND (localisation clause) AND (fusion clause)",
      "count": 0,
      "bound_not_reproducible_as_stored": "NOT REPRODUCIBLE AS STORED, flagged 2026-09-23. This `query` field records a SUMMARY of the search rather than the search: the clause text it names was never written down, so the string cannot be re-run and this bound could not be included in the cycle-71 audit that re-ran 40 of the corpus's other zero-bounds against the live index (all 40 still returned zero). The clauses have deliberately NOT been reconstructed - guessing them would manufacture a query that was never run, which is worse than an abbreviated one because it would look auditable. This flag does not dispute the count or the absence; it records that this particular bound is not independently checkable."
    }
  ],
  "reading": "Titles and abstracts only (brief rule 80). Recorded so the NOT APPLICABLE determination is auditable: 83 records on this gene and a clean zero on every subnuclear and fusion query. This entry already notes FUT9 is the cleanest identifier on its beat - no gene synonyms, no HGNC previous symbols - so unlike most genes in this tranche there is no alias route that could rescue a zero, and the retired-symbol question does not arise.",
  "absence_class": "not-applicable"
}